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子宫内膜组合体模型揭示了通过雌激醇驱动的WNT7B抑制来调节子宫内膜腺发育
Xintong Li1, Yanjie Guo1, Jianlin Li1,2
1Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong SAR, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 23, 2025
概括
研究人员开发了人类子宫内膜的3D模型,以研究腺体发育. 他们发现WNT7B抑制了腺体形成,这一过程受到雌激醇和TGFβ1信号的影响,为子宫内膜异常提供了新的治疗点.
科学领域:
- 生殖生物学 生殖生物学
- 发展生物学 发展生物学
- 3D 有机体模型
背景情况:
- 成年子宫内膜腺循环再生,对生殖至关重要,但发育机制尚不清楚.
- 现有的3D子宫内膜模型不能完全复制人体腺体发育在体外.
研究的目的:
- 建立一个强大的3D子宫内膜组合体模型,用于研究腺体发育.
- 确定子宫内膜腺形成和发育的关键分子调节剂.
主要方法:
- 将人类子宫内膜器官有机体 (EO) 和人类子宫内膜层细胞 (HESC) 集成到一个3D组合体模型中.
- 转录组分析以确定调节分子.
- 使用WNT7B淘汰赛小鼠进行体内验证,以及用雌激醇刺激进行体内/体内研究.
主要成果:
- 3D组合体模型成功复制了管状腺的形成和树皮-上皮相互作用.
- 确定Wnt家族成员7B (WNT7B) 是腺体发育的内在抑制剂.
- 发现TGFβ1信号传递,VDR相互作用和雌激素调节了WNT7B和腺体形成.
结论:
- 雌激醇抑制WNT7B,促进腺体的形成,而TGFβ1-VDR交叉影响这个过程.
- 这项研究阐明了子宫内膜腺发育中的关键信号通路.
- 这些发现为改进3D子宫内膜模型和治疗子宫内膜异位症和不孕症等疾病的潜在治疗点提供了基础.
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